• 【T6SS-Dependent猎物细胞裂解后的DNA吸收会诱导SOS反应并降低baylyi不动杆菌的适应性。】 复制标题 收藏 收藏
    DOI:10.1016/j.celrep.2019.09.083 复制DOI
    作者列表:Lin L,Ringel PD,Vettiger A,Dürr L,Basler M
    BACKGROUND & AIMS: :Certain Gram-negative bacteria use the type VI secretion system (T6SS) to kill and lyse competing bacteria. Here, we show that the T6SS-dependent lysis of prey cells by the naturally competent Acinetobacter baylyi results in the extensive filamentation of a subpopulation of A. baylyi cells. Filamentation is dependent on the release of DNA from the prey and its uptake by the competence system. The analysis of A. baylyi transcriptome and the response of transcriptional reporters suggest that the uptake of DNA results in the upregulation of the SOS response, which often leads to cell-division arrest. Long-term competition between competent and non-competent strains shows that the strain lacking the DNA uptake machinery outcompetes the parental strain only in the presence of the T6SS-dependent lysis of prey cells. Our data suggest that the cost of the induced SOS response may drive the selection of tight regulation or the loss of DNA uptake in bacteria capable of lysing their competitors.
    背景与目标: : 某些革兰氏阴性细菌使用VI型分泌系统 (T6SS) 杀死和裂解竞争细菌。在这里,我们表明,天然感受态不动杆菌baylyi对猎物细胞的T6SS-dependent裂解导致a.baylyi细胞亚群的广泛丝状化。丝状化取决于猎物中DNA的释放及其能力系统的吸收。对A. baylyi转录组的分析和转录报告者的反应表明,DNA的摄取导致SOS反应的上调,这通常导致细胞分裂停滞。胜任菌株和非胜任菌株之间的长期竞争表明,缺乏DNA吸收机制的菌株仅在存在猎物细胞的T6SS-dependent裂解的情况下才胜过亲本菌株。我们的数据表明,诱导的SOS反应的成本可能会导致选择严格的调节或丧失能够裂解其竞争对手的细菌中的DNA吸收。
  • 【阿拉伯联合酋长国耐碳青霉烯和OXA-23-producing鲍曼不动杆菌分离株。】 复制标题 收藏 收藏
    DOI:10.1111/j.1469-0691.2008.02056.x 复制DOI
    作者列表:Mugnier P,Poirel L,Pitout M,Nordmann P
    BACKGROUND & AIMS: :Five carbapenem-resistant Acinetobacter baumannii isolates, collected from the United Arab Emirates in 2006, were investigated to identify the mechanism(s) responsible for carbapenem resistance. Genotyping was performed by pulsed-field gel electrophoresis, and the location of the bla(OXA-23) gene was determined by using the endonuclease I CeuI technique and mating-out assays. The four isolates in which the bla(OXA-23) gene was located on the chromosome within a Tn2006 composite transposon were clonally related. The single non-clonally related isolate harboured the bla(OXA-23) gene on a 70-kb transferable plasmid. This study reports on the dissemination of OXA-23-producing A. baumannii isolates in the Middle East.
    背景与目标: : 研究了从阿拉伯联合酋长国2006年收集的五种耐碳青霉烯类鲍曼不动杆菌分离株,以确定引起碳青霉烯类耐药的机制。通过脉冲场凝胶电泳进行基因分型,并通过使用内切核酸酶I ceeu技术和交配试验确定bla(OXA-23) 基因的位置。其中bla(OXA-23) 基因位于Tn2006复合转座子内染色体上的四个分离株是克隆相关的。单个非克隆相关分离物将bla(OXA-23) 基因保存在70kb可转移质粒上。本研究报告了OXA-23-producing鲍曼不动杆菌分离株在中东的传播情况。
  • 【不动杆菌属的整合子基因盒。来自华南的菌株。】 复制标题 收藏 收藏
    DOI:10.1016/j.ijantimicag.2008.05.014 复制DOI
    作者列表:Xu X,Kong F,Cheng X,Yan B,Du X,Gai J,Ai H,Shi L,Iredell J
    BACKGROUND & AIMS: :The epidemiology of emerging antibiotic resistance genes in Asia is inadequately defined and studies within the major pools of transmissible genes such as integron gene cassettes are important. One hundred and twenty-two non-repetitive Acinetobacter spp. isolates were obtained from inpatients of a major hospital in South China. Fifty-three of these isolates contained class 1 integrons, and there is evidence of horizontal gene transfer between unrelated clones. The common pool of gene cassettes was dominated by four cassette arrays: arr3-aacA4 (24 isolates of several unrelated strains); aacC1-orfP-orfQ-aadA1a (11 isolates, probably all the same strain); aacA4-catB8-aadA1 (2 isolates); and dfrVII (1 isolate). We developed a simple restriction fragment length polymorphism (RFLP)-based identification of these and other cassettes reported in China, using readily available enzymes, to facilitate further studies of this type.
    背景与目标: : 亚洲新兴抗生素抗性基因流行病学定义不充分,在整合子基因盒等主要可传播基因库中的研究很重要。122种非重复不动杆菌属。分离株是从华南一家大型医院的住院患者中获得的。这些分离株中有53个包含1类整合子,并且有证据表明不相关克隆之间存在水平基因转移。基因盒的共同库主要由四个盒阵列组成: arr3-aacA4 (几个无关菌株的24个分离株); aacC1-orfP-orfQ-aadA1a (11个分离株,可能都是相同的菌株); aacA4-catB8-aadA1 (2个分离株); 和dfrVII (1个分离株)。我们开发了一种基于简单限制性片段长度多态性 (RFLP) 的中国报道的这些和其他盒的鉴定,使用现成的酶,以促进对这种类型的进一步研究。
  • 【米诺环素和粘菌素组合对亚胺培南耐药鲍曼不动杆菌临床分离株的体外作用。】 复制标题 收藏 收藏
    DOI:10.1093/jac/dkm178 复制DOI
    作者列表:Tan TY,Ng LS,Tan E,Huang G
    BACKGROUND & AIMS: OBJECTIVES:The study investigated the effect of colistin and minocycline when tested singly and in combination against Acinetobacter baumannii. METHODS:Thirteen unrelated imipenem-resistant A. baumannii clinical isolates were included in the study. MICs of colistin sulphate and minocycline were determined by broth macrodilution and Etest. Organisms were also tested against the two antibiotics singly and in combination using time-kill methods and an Etest-based method. RESULTS:Neither colistin nor minocycline when tested alone demonstrated bactericidal activity. However, the combination of colistin and minocycline demonstrated bactericidal activity against most of the isolates tested. At 24 h, the combination of antibiotics demonstrated synergy in 12 of the 13 isolates by time-kill methods. None of the isolates demonstrated synergy by Etest methods. CONCLUSIONS:The combination of colistin and minocycline was found to be bactericidal and synergistic against A. baumannii by time-kill methods. There was no agreement between time-kill and Etest methods for synergy testing.
    背景与目标:
  • 【NLRP3炎症体介导鲍曼不动杆菌反应免疫细胞中白细胞介素-1β 的产生,并促进小鼠肺部炎症。】 复制标题 收藏 收藏
    DOI:10.1111/imm.12704 复制DOI
    作者列表:Kang MJ,Jo SG,Kim DJ,Park JH
    BACKGROUND & AIMS: :Acinetobacter baumannii is a multi-drug resistant, Gram-negative bacteria and infection with this organism is one of the major causes of mortality in intensive care units. Inflammasomes are multiprotein oligomers that include caspase-1, and their activation is required for maturation of interleukin-1β (IL-1β). Inflammasome signalling is involved in host defences against various microbial infections, but the precise mechanism by which A. baumannii activates inflammasomes and the roles of relevant signals in host defence against pulmonary A. baumannii infection are unknown. Our results showed that NLRP3, ASC and caspase-1, but not NLRC4, are required for A. baumannii-induced production of IL-1β in macrophages. An inhibitor assay revealed that various pathways, including P2X7R, K+ efflux, reactive oxygen species production and release of cathepsins, are involved in IL-1β production in macrophages in response to A. baumannii. Interleukin-1β production in bronchoalveolar lavage (BAL) fluid was impaired in NLRP3-deficient and caspase-1/11-deficient mice infected with A. baumannii, compared with that in wild-type (WT) mice. However, the bacterial loads in BAL fluid and lungs were comparable between WT and NLRP3-deficient or caspase-1/11-deficient mice. The severity of lung pathology was reduced in NLRP3- deficient, caspase-1/11- deficient and IL-1-receptor-deficient mice, although the recruitment of immune cells and production of inflammatory cytokines and chemokines were not altered in these mice. These findings indicate that A. baumannii leads to the activation of NLRP3 inflammasome, which mediates IL-1β production and lung pathology.
    背景与目标: : 鲍曼不动杆菌是一种多重耐药的革兰氏阴性细菌,感染这种生物是重症监护病房死亡的主要原因之一。炎性小体是包括caspase-1的多蛋白低聚物,它们的活化是白介素-1β (IL-1β) 成熟所必需的。炎症小体信号参与宿主防御各种微生物感染,但鲍曼不动杆菌激活炎症小体的确切机制以及相关信号在宿主防御肺鲍曼不动杆菌感染中的作用尚不清楚。我们的结果表明,鲍曼不动杆菌诱导的巨噬细胞中IL-1β 的产生需要NLRP3,ASC和caspase-1,而不是NLRC4。抑制剂分析显示,各种途径,包括P2X7R,K外排,活性氧的产生和组织蛋白酶的释放,都参与了响应鲍曼不动杆菌的巨噬细胞中IL-1β 的产生。与野生型 (WT) 小鼠相比,感染鲍氏不动杆菌的NLRP3-deficient和caspase-1/11缺陷小鼠的支气管肺泡灌洗液 (BAL) 中白细胞介素-1β 的产生受到损害。然而,BAL液和肺中的细菌负荷在WT和NLRP3-deficient或caspase-1/11缺陷小鼠之间是相当的。尽管在这些小鼠中免疫细胞的募集以及炎性细胞因子和趋化因子的产生没有改变,但在NLRP3缺陷,caspase-1/11缺陷和IL-1-receptor-deficient小鼠中肺病理的严重程度降低。这些发现表明鲍曼不动杆菌导致NLRP3炎症小体的激活,从而介导IL-1β 的产生和肺部病理。
  • 【在中国西部爆发了耐碳青霉烯的鲍曼不动杆菌产生OXA-23碳青霉烯酶。】 复制标题 收藏 收藏
    DOI:10.1016/j.ijantimicag.2007.08.019 复制DOI
    作者列表:Zong Z,Lü X,Valenzuela JK,Partridge SR,Iredell J
    BACKGROUND & AIMS: :Twenty-two non-repetitive carbapenem-resistant Acinetobacter baumannii isolates were obtained from Intensive Care Unit patients. All of the isolates carried bla(OXA-23), bla(OXA-66), a novel cephalosporinase-encoding gene (bla(ADC-25)) and a class 1 integron with an aacC1-orfP-orfQ-aadA1a cassette array and had identical enterobacterial repetitive intergenic consensus (ERIC) profiles. ISAba1 was found upstream of bla(OXA-23), but was not associated with bla(OXA-66) or bla(ADC-25).
    背景与目标: : 从重症监护病房患者中获得了22株非重复的耐碳青霉烯类鲍曼不动杆菌分离株。所有分离株均携带bla(OXA-23),bla(OXA-66),新型头孢菌素酶编码基因 (bla(ADC-25)) 和具有aacC1-orfP-orfQ-aadA1a盒阵列的1类整合子,并具有相同的肠细菌重复基因间共识 (ERIC) 谱。ISAba1位于bla(OXA-23) 的上游,但与bla(OXA-66) 或bla(ADC-25) 无关。
  • 【[摩洛哥大学医院鲍曼不动杆菌菌株的流行和体外抗菌敏感性模式]。】 复制标题 收藏 收藏
    DOI:10.1016/j.medmal.2007.05.006 复制DOI
    作者列表:Lahsoune M,Boutayeb H,Zerouali K,Belabbes H,El Mdaghri N
    BACKGROUND & AIMS: OBJECTIVE:The aim of this study was to identify the clinical presentations and the current antimicrobial susceptibility of Acinetobacter baumannii. RESULTS:We identified 754 strains especially from intensive care units (50.53%) between January 2003 and December 2005. Bronchial swabs and blood culture were prevalent. High-level resistance to betalactamines was noted: 91% to cefotaxime, 50.3% to ceftazidime, and 42.6% to imipenem. Aminoside resistance varied from 17.9% for netilmicine to 72.1% for gentamycin. The resistance rate to ciprofloxacine was 65.8%, and to trimethoprime-sulfamethoxazole 75.8%. In intensive care units, the antimicrobial resistance rate of A. baumannii was higher (p<0.05). CONCLUSION:The resistance of A. baumannii to current antibiotics is alarming especially in intensive care units. An effective strategy against nosocomial infection is still necessary.
    背景与目标:
  • 【鲍曼不动杆菌的Trehalose-6-phosphate-mediated表型变化。】 复制标题 收藏 收藏
    DOI:10.1111/1462-2920.15148 复制DOI
    作者列表:Hubloher JJ,Zeidler S,Lamosa P,Santos H,Averhoff B,Müller V
    BACKGROUND & AIMS: :The stress protectant trehalose is synthesized in Acinetobacter baumannii from UPD-glucose and glucose-6-phosphase via the OtsA/OtsB pathway. Previous studies proved that deletion of otsB led to a decreased virulence, the inability to grow at 45°C and a slight reduction of growth at high salinities indicating that trehalose is the cause of these phenotypes. We have questioned this conclusion by producing ∆otsA and ∆otsBA mutants and studying their phenotypes. Only deletion of otsB, but not deletion of otsA or otsBA, led to growth impairments at high salt and high temperature. The intracellular concentrations of trehalose and trehalose-6-phosphate were measured by NMR or enzymatic assay. Interestingly, none of the mutants accumulated trehalose any more but the ∆otsB mutant with its defect in trehalose-6-phosphate phosphatase activity accumulated trehalose-6-phosphate. Moreover, expression of otsA in a ∆otsB background under conditions where trehalose synthesis is not induced led to growth inhibition and the accumulation of trehalose-6-phosphate. Our results demonstrate that trehalose-6-phosphate affects multiple physiological activities in A. baumannii ATCC 19606.
    背景与目标: : 压力保护剂海藻糖由UPD-葡萄糖和glucose-6-phosphase通过OtsA/OtsB途径在鲍曼不动杆菌中合成。先前的研究证明,otsB的缺失导致毒力降低,在45 °C下无法生长以及在高盐度下的生长略有降低,这表明海藻糖是这些表型的原因。我们通过产生 ∆ otsa和 ∆ otsba突变体并研究其表型来质疑这一结论。仅删除otsB,而不删除otsA或otsBA,在高盐和高温下导致生长受损。通过NMR或酶法测定海藻糖和trehalose-6-phosphate的细胞内浓度。有趣的是,除了trehalose-6-phosphate磷酸酶活性缺陷的 ∆ otsb突变体外,没有一个突变体再积累海藻糖trehalose-6-phosphate。此外,在不诱导海藻糖合成的条件下,otsA在 ∆ otsb背景中的表达导致生长抑制和trehalose-6-phosphate积累。我们的结果表明,trehalose-6-phosphate影响鲍曼不动杆菌ATCC 19606的多种生理活动。
  • 【在塞尔维亚恢复的鲍曼不动杆菌的第一个全国性多中心研究: OXA-72,OXA-23和NDM-1-producing分离株的出现。】 复制标题 收藏 收藏
    DOI:10.1186/s13756-020-00769-8 复制DOI
    作者列表:Lukovic B,Gajic I,Dimkic I,Kekic D,Zornic S,Pozder T,Radisavljevic S,Opavski N,Kojic M,Ranin L
    BACKGROUND & AIMS: BACKGROUND:The worldwide emergence and clonal spread of carbapenem-resistant Acinetobacter baumannii (CRAB) is of great concern. The aim of this nationwide study was to investigate the prevalence of CRAB isolates in Serbia and to characterize underlying resistance mechanisms and their genetic relatedness. METHODS:Non-redundant clinical samples obtained from hospitalized patients throughout Serbia were included in the prospective, observational, multicenter study conducted from January to June 2018. Samples were initially screened for the presence of Acinetobacter baumannii-calcoaceticus (Acb) complex using conventional bacteriological techniques. Acb complexes recovered from clinical samples obtained from inpatients with confirmed bacterial infections were further evaluated for the presence of A. baumannii. Identification to the species level was done by the detection of the blaOXA-51 gene and rpoB gene sequence analysis. Susceptibility testing was done by disk diffusion and broth microdilution method. CRAB isolates were tested for the presence of acquired carbapenemases (blaOXA-24-like, blaOXA-23-like,blaOXA-58-like, blaOXA-143-like, blaIMP, blaVIM, blaGIM, blaSPM, blaSIM, blaNDM) by PCR. Clonal relatedness was assessed by pulsed-field gel electrophoresis (PFGE) and multilocus sequence typing (MLST). RESULTS:Acb complex was isolated in 280 out of 2401 clinical samples (11.6%). Overall, A. baumannii was identified in 237 out of 280 Acb complex (84.6%). CRAB prevalence was found to be 93.7% (237/222). The MIC50/MIC90 for imipenem and meropenem were 8/> 32 μg/mL and 16/> 32 μg/mL, respectively. Although susceptibility was high for colistin (95.7%; n = 227) and tigecycline (75.1%; n = 178), ten isolates (4.3%) were classified as pandrug-resistant. The following carbapenemases-encoding genes were found: 98 (44.2%) blaOXA-24-like, 76 (34.5%) blaOXA-23-like, and 7 (3.2%) blaNDM-1. PFGE analysis revealed six different clusters. MLST analysis identified three STs: ST2 (n = 13), ST492 (n = 14), and ST636 (n = 10). Obtained results evaluated that circulating CRAB clones in Serbia were as follows: blaOXA66/blaOXA23/ST2 (32.4%), blaOXA66/blaOXA23/blaOXA72/ST2 (2.7%), blaOXA66/blaOXA72/ST492 (37.8%), and blaOXA66/blaOXA72/ST636 (27.1%). CONCLUSION:This study revealed extremely high proportions of carbapenem resistance among A. baumannii clinical isolates due to the emergence of blaOXA-72, blaOXA-23, and blaNDM-1 genes among CRAB isolates in Serbia and their clonal propagation.
    背景与目标:
  • 【决定水杨酸酯分解代谢的sal基因是不动杆菌属菌株adp1中分解代谢基因簇的一部分。】 复制标题 收藏 收藏
    DOI:10.1128/jb.182.7.2018-2025.2000 复制DOI
    作者列表:Jones RM,Pagmantidis V,Williams PA
    BACKGROUND & AIMS: :A 5-kbp region upstream of the are-ben-cat genes was cloned from Acinetobacter sp. strain ADP1, extending the supraoperonic cluster of catabolic genes to 30 kbp. Four open reading frames, salA, salR, salE, and salD, were identified from the nucleotide sequence. Reverse transcription-PCR studies suggested that these open reading frames are organized into two convergent transcription units, salAR and salDE. The salE gene, encoding a protein of 239 residues, was ligated into expression vector pET5a. Its product, SalE, was shown to have esterase activity against short-chain alkyl esters of 4-nitrophenol but was also able to hydrolyze ethyl salicylate to ethanol and salicylic acid. A mutant of ADP1 with a Km(r) cassette introduced into salE had lost the ability to utilize only ethyl and methyl salicylates of the esters tested as sole carbon sources, and no esterase activity against ethyl salicylate could be detected in cell extracts. SalE was induced during growth on ethyl salicylate but not during growth on salicylate itself. salD encoded a protein of undetermined function with homologies to the Escherichia coli FadL membrane protein, which is involved in facilitating fatty acid transport, and a number of other proteins detected during aromatic catabolism, which may also function in hydrocarbon transport or uptake processes. A Km(r) cassette insertion in salD deleteriously affected cell growth and viability. The salA and salR gene products closely resemble two Pseudomonas proteins, NahG and NahR, respectively encoding salicylate hydroxylase and the LysR family regulator of both salicylate and naphthalene catabolism. salA was cloned into pUC18 together with salR and salE, and its gene product showed salicylate-inducible hydroxylase activity against a range of substituted salicylates, with the same relative specific activities as found in wild-type ADP1 grown on salicylate. Mutations involving insertion of Km(r) cassettes into salA and salR eliminated expression of salicylate hydroxylase activity and the ability to grow on either salicylate or ethyl salicylate. Studies of mutants with disruptions of genes of the beta-ketoadipate pathway with or without an additional salE mutation confirmed that ethyl salicylate and salicylate were channeled into the beta-ketoadipate pathway at the level of catechol and thence dissimilated by the cat gene products. SalR appeared to regulate expression of salA but not salE.
    背景与目标: : 从不动杆菌属中克隆了一个位于ar-ben-cat基因上游的5-kbp区域。菌株ADP1,将分解代谢基因簇的上周期扩展到30 kbp。从核苷酸序列中鉴定出四个开放阅读框,salA,salR,salE和salD。逆转录PCR研究表明,这些开放阅读框被组织成两个会聚的转录单位,salAR和salDE。将编码239残基蛋白的salE基因连接到表达载体pET5a中。它的产品SalE显示出对4-硝基苯酚的短链烷基酯具有酯酶活性,但也能够将水杨酸乙酯水解为乙醇和水杨酸。引入salE的带有Km(r) 盒的ADP1突变体失去了仅利用测试的酯的乙基和水杨酸甲酯作为唯一碳源的能力,并且在细胞提取物中未检测到对水杨酸乙酯的酯酶活性。在水杨酸乙酯的生长过程中会诱导销售,但在水杨酸乙酯本身的生长过程中不会诱导销售。salD编码一种功能未定的蛋白质,与大肠杆菌FadL膜蛋白具有同源性,该蛋白参与促进脂肪酸转运,以及在芳香族分解代谢过程中检测到的许多其他蛋白质,这些蛋白质也可能在碳氢化合物转运或吸收过程中起作用。在salD中插入Km(r) 盒会严重影响细胞的生长和活力。salA和salR基因产物与两个假单胞菌蛋白NahG和NahR非常相似,分别编码水杨酸盐羟化酶和水杨酸盐和萘分解代谢的LysR家族调节剂。salA与salR和salE一起被克隆到pUC18中,其基因产物对一系列取代的水杨酸盐显示出水杨酸盐诱导的羟化酶活性,其相对比活与在水杨酸盐上生长的野生型ADP1中发现的相对比活相同。涉及将Km(r) 盒插入salA和salR的突变消除了水杨酸羟化酶活性的表达以及在水杨酸酯或水杨酸乙酯上生长的能力。对具有或没有附加销售突变的 β-酮己二酸途径基因破坏的突变体的研究证实,水杨酸乙酯和水杨酸乙酯在邻苯二酚的水平下被引导进入 β-酮己二酸途径,然后被cat基因产物异化。SalR似乎可以调节salA的表达,但不能调节销售。
  • 【从外科重症监护病房分离的鲍曼不动杆菌的流行病学分析。】 复制标题 收藏 收藏
    DOI: 复制DOI
    作者列表:Ben Hassen A,van der-Mee Marquet N,Guedira S,Bouabdallah F,Houissa M,Ennigrou S,Ben Hamida A,Audurier A,Ben Redjeb S
    BACKGROUND & AIMS: A serious epidemic of Acinetobacter baumannii resistant to imipenem occurred in the surgical intensive care unit of the hospital Charles-Nicolle in Tunis during February 1994, causing two deaths among three patients. The Acinetobacter strains were isolated from various samples of the intensive care unit. The techniques used for typing were biotyping, antibiogram, plasmid profiles and chromosomal DNA by random amplified polymorphic DNA (RAPD). The A baumannii strains isolated from patients exhibited an identical pattern with all the epidemiological markers utilized; the strains from the surrounding areas showed four and six different patterns respectively for phenotypic and genotypic characters. The strain isolated from a care table had the same phenotypic and genotypic pattern as that of the patients' strains.

    背景与目标: 1994年2月期间,突尼斯Charles-Nicolle医院的外科重症监护室发生了对亚胺培南耐药的鲍曼不动杆菌的严重流行,导致三名患者中有两人死亡。从重症监护病房的各种样品中分离出不动杆菌菌株。用于分型的技术是通过随机扩增多态性DNA (RAPD) 进行的生物分型,抗生素图,质粒谱和染色体DNA。从患者中分离出的鲍曼不动杆菌菌株表现出与所有使用的流行病学标记相同的模式; 来自周围地区的菌株分别表现出四种和六种不同的表型和基因型特征。从护理表中分离出的菌株具有与患者菌株相同的表型和基因型模式。
  • 【鲍曼不动杆菌接受替加环素时血流感染: 一项警示报告。】 复制标题 收藏 收藏
    DOI:10.1093/jac/dkl441 复制DOI
    作者列表:Peleg AY,Potoski BA,Rea R,Adams J,Sethi J,Capitano B,Husain S,Kwak EJ,Bhat SV,Paterson DL
    BACKGROUND & AIMS: OBJECTIVES:Tigecycline has shown in vitro activity against Acinetobacter baumannii. Yet, published clinical experience with tigecycline use outside clinical trials is lacking. We describe, for the first time, bloodstream infection caused by tigecycline-non-susceptible A. baumannii occurring in patients receiving tigecycline for other indications. The possible mechanisms of resistance and pharmacokinetic limitations of the drug are addressed. METHODS:The clinical records of involved patients were systematically reviewed. Tigecycline susceptibility testing was initially performed using the Etest method and confirmed by agar dilution. Involved isolates underwent PFGE and exposure to phenyl-arginine-beta-naphthylamide (PAbetaN), an efflux pump inhibitor. RESULTS:Two patients developed A. baumannii bloodstream infection while receiving tigecycline. Tigecycline was administered for other indications for 9 and 16 days, respectively, before the onset of A. baumannii infection. Patient 1 died of overwhelming A. baumannii infection and Patient 2 recovered after a change in antibiotic therapy. The MICs of tigecycline were 4 and 16 mg/L, respectively. Both isolates had a multidrug-resistant phenotype and were genotypically unrelated. After exposure to PAbetaN, the MICs reduced to 1 and 4 mg/L, respectively. CONCLUSIONS:To our knowledge, this is the first clinical description of bloodstream infection caused by tigecycline-non-susceptible A. baumannii. Such resistance appears to be at least partly attributable to an efflux pump mechanism. Given the reported low serum tigecycline levels, we urge caution when using this drug for treatment of A. baumannii bloodstream infection.
    背景与目标:
  • 【不动杆菌属错配修复基因mutS的功能。菌株adp1。】 复制标题 收藏 收藏
    DOI:10.1128/JB.183.23.6822-6831.2001 复制DOI
    作者列表:Young DM,Ornston LN
    BACKGROUND & AIMS: :The genus Acinetobacter encompasses a heterogeneous group of bacteria that are ubiquitous in the natural environment due in part to their ability to adapt genetically to novel challenges. Acinetobacter sp. strain ADP1 (also known as strain BD413) is naturally transformable and takes up DNA from any source. Donor DNA can be integrated into the chromosome by recombination provided it possesses sufficient levels of nucleotide sequence identity to the recipient's DNA. In other bacteria, the requirement for sequence identity during recombination is partly due to the actions of the mismatch repair system, a key component of which, MutS, recognizes mismatched bases in heteroduplex DNA and, along with MutL, blocks strand exchange. We have cloned mutS from strain ADP1 and examined its roles in preventing recombination between divergent DNA and in the repair of spontaneous replication errors. Inactivation of mutS resulted in 3- to 17-fold increases in transformation efficiencies with donor sequences that were 8 to 20% divergent relative to the strain ADP1. Strains lacking MutS exhibited increased spontaneous mutation frequencies, and reversion assays demonstrated that MutS preferentially recognized transition mismatches while having little effect on the repair of transversion mismatches. Inactivation of mutS also abolished the marker-specific variations in transforming efficiency seen in mutS(+) recipients where transition and frameshift alleles transformed at eightfold lower frequencies than transversions or large deletions. Comparison of the MutS homologs from five individual Acinetobacter strains with those of other gram-negative bacteria revealed that a number of unique indels are conserved among the Acinetobacter amino acid sequences.
    背景与目标: : 不动杆菌属包括一群在自然环境中普遍存在的异质细菌,部分原因是它们能够在基因上适应新的挑战。不动杆菌属。ADP1菌株 (也称为BD413菌株) 是天然可转化的,并从任何来源获取DNA。只要供体DNA与受体DNA具有足够水平的核苷酸序列同一性,就可以通过重组将其整合到染色体中。在其他细菌中,重组过程中对序列同一性的要求部分是由于错配修复系统的作用,该系统的关键组成部分MutS识别异双链DNA中的错配碱基,并与MutL一起阻止链交换。我们已经从ADP1菌株中克隆了mutS,并检查了其在防止发散DNA之间的重组以及修复自发复制错误中的作用。mutS的失活导致转化效率提高3至17倍,供体序列相对于菌株adp1发散8至20% 倍。缺乏MutS的菌株表现出增加的自发突变频率,并且逆转试验表明,MutS优先识别过渡失配,而对逆转失配的修复几乎没有影响。mutS的失活还消除了在mutS () 受体中看到的特定于标记的转换效率变化,其中转换和移码等位基因的转换频率比转换或大缺失低八倍。将五个单独的不动杆菌菌株的MutS同源物与其他革兰氏阴性细菌的MutS同源物进行比较,发现不动杆菌氨基酸序列中存在许多独特的indels。
  • 【通过DNA-DNA杂交鉴定的不动杆菌菌株的抗菌敏感性。】 复制标题 收藏 收藏
    DOI: 复制DOI
    作者列表:Tjernberg I
    BACKGROUND & AIMS: :The in vitro activity of 21 antimicrobial agents against 143 Acinetobacter strains (belonging to 12 different DNA hybridization groups) was studied. Of the antibiotics tested, ciprofloxacin, ofloxacin, doxycycline and imipenem had the lowest MICs. For most antibiotics there was a considerable overlap of the MICs between the DNA groups; however, some differences in antimicrobial susceptibility between DNA groups were found. Strains of DNA groups 2 (A. baumannii) and 13 (unnamed) were most resistant, and strains of DNA groups 8 (A. lwoffii) and 5 (A. junii) less resistant. Many DNA groups contain both saccharolytic and non-saccharolytic strains but in the present study no differences in antimicrobial susceptibility were found between strains of a particular DNA group with regard to this property.
    背景与目标: : 研究了21种抗菌剂对143不动杆菌菌株 (属于12个不同的DNA杂交组) 的体外活性。在测试的抗生素中,环丙沙星,氧氟沙星,强力霉素和亚胺培南的mic最低。对于大多数抗生素,DNA组之间的mic有相当大的重叠; 但是,发现DNA组之间的抗菌药物敏感性存在一些差异。DNA组2 (鲍曼不动杆菌) 和13 (未命名) 的菌株抗性最高,而DNA组8 (A. lwoffii) 和5 (A. junii) 的菌株抗性较低。许多DNA组同时包含糖分解和非糖分解菌株,但在本研究中,就该特性而言,特定DNA组的菌株之间未发现抗菌药物敏感性差异。
  • 【一种短D-对映体抗菌肽,对多重耐药铜绿假单胞菌和鲍曼不动杆菌具有有效的免疫调节和抗生物膜活性。】 复制标题 收藏 收藏
    DOI:10.1038/s41598-017-07440-0 复制DOI
    作者列表:Mohamed MF,Brezden A,Mohammad H,Chmielewski J,Seleem MN
    BACKGROUND & AIMS: :Antimicrobial peptides (AMPs) represent a promising therapeutic alternative for the treatment of antibiotic-resistant bacterial infections. The present study investigates the antimicrobial activity of new, rationally-designed derivatives of a short α-helical peptide, RR. From the peptides designed, RR4 and its D-enantiomer, D-RR4, emerged as the most potent analogues with a more than 32-fold improvement in antimicrobial activity observed against multidrug-resistant strains of Pseudomonas aeruginosa and Acinetobacter baumannii. Remarkably, D-RR4 demonstrated potent activity against colistin-resistant strains of P. aeruginosa (isolated from cystic fibrosis patients) indicating a potential therapeutic advantage of this peptide over several AMPs. In contrast to many natural AMPs, D-RR4 retained its activity under challenging physiological conditions (high salts, serum, and acidic pH). Furthermore, D-RR4 was more capable of disrupting P. aeruginosa and A. baumannii biofilms when compared to conventional antibiotics. Of note, D-RR4 was able to bind to lipopolysaccharide to reduce the endotoxin-induced proinflammatory cytokine response in macrophages. Finally, D-RR4 protected Caenorhabditis elegans from lethal infections of P. aeruginosa and A. baumannii and enhanced the activity of colistin in vivo against colistin-resistant P. aeruginosa.
    背景与目标: 抗菌肽 (AMPs) 是治疗抗生素耐药性细菌感染的一种有前途的治疗选择。本研究调查了短 α-螺旋肽RR的新的,合理设计的衍生物的抗菌活性。从设计的肽中,RR4及其D-对映异构体D-RR4成为最有效的类似物,对铜绿假单胞菌和鲍曼不动杆菌的多重耐药菌株的抗菌活性提高了32倍以上。值得注意的是,D-RR4显示出对铜绿假单胞菌 (从囊性纤维化患者中分离出) 的粘菌素抗性菌株的有效活性,表明该肽在几种AMPs上具有潜在的治疗优势。与许多天然amp相比,D-RR4在具有挑战性的生理条件 (高盐、血清和酸性pH) 下保持其活性。此外,与常规抗生素相比,D-RR4更有能力破坏铜绿假单胞菌和鲍曼不动杆菌生物膜。值得注意的是,D-RR4能够与脂多糖结合以减少巨噬细胞中内毒素诱导的促炎性细胞因子反应。最后,D-RR4保护秀丽隐杆线虫免受铜绿假单胞菌和鲍曼不动杆菌的致命感染,并增强粘菌素在体内抵抗粘菌素抗性铜绿假单胞菌的活性。

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